1. Field of the Invention
The present invention pertains to optical inspection of products produced during automated manufacturing. More particularly, this invention relates to a method for tagging semi-transparent polymeric layers contained in a multilayer sensor structure in order to facilitate optical inspection and alignment of the layers.
2. Description of the Related Art
In the health care field, particularly in the area of clinical diagnostics, ion-selective-electrode (ISE) sensors are commonly used to measure the activity or concentration of various ions and metabolites present in biological fluids. ISE sensors employ potentiometric or amperiometric electrochemical processes which generate potential or current signals that are related to the activity of an ion of interest in a sample. For example, ISE sensors are typically used to determine chloride, potassium, lithium, calcium, magnesium, carbonate, hydrogen, and sodium ion content in such fluids. Generally, the signal generated within the sensor is linearly dependent on the logarithm of the activity of the ion of interest for potentiometric analyses. The activity of an ion of interest is defined as its concentration multiplied by an activity coefficient, where the activity coefficient is generally known or is available in the art.
Typically, solid state ISE sensors use a solid membrane as a sensing element or electrode, the membrane being highly selective to the ionic species being sought and reacting to the ionic species with changes in ionic conductivity. In addition, conventional ISE sensors may contain an internal reference electrode. In operation, one surface of the sensing membrane is immersed in a biological sample solution of ions for which it is selective whereby a potential develops across the membrane surface at the interface of the solution and the membrane. In a potentiometric sensor, this potential varies with the concentration of ions in solution and its magnitude is measured as a voltage. By comparing the voltage generated at the sensing membrane surface with that generated by a reference electrode using a reference ionic solution, it is possible to calculate the concentration of the ionic species being sought. The desired selectivity is often achieved by incorporating into the membrane of an ion-selective electrode an ion selective agent such as an ionophore to increase the permeability of cell membranes to a specific ion. Generally, ion-selective membranes are formed from a heavily plasticized polymer matrix, such as polyvinyl chloride, which contains the ionophore selective for the ion of interest. For example, the ionophore valinomycin has been incorporated into a layer of membrane selective for potassium ions; trifluoroacetyl-p-butylbenzene or other trifluoroacetophenone derivatives have been used as ionophores selective for carbonate ions.
By "biological sample" is meant any fluid of biological origin including fluids of biological origin which have been chemically and/or physically treated, diluted, or concentrated prior to analysis. Examples of biological samples include serum, urine, plasma, whole blood, cerebrospinal fluid, amniotic fluid, saliva and tears.
A general discussion of the principles of ISE sensors is provided by Foreman et al., "Ion Selective Electrodes", Automatic Chemical Analysis, Ellis Horwell Ltd., Chichester, England (1975). ISE sensors can be classified according to the nature of the membrane material, and include solid state membrane electrodes, glass membrane electrodes, liquid membrane electrodes having charged ion-selective agents, and neutral liquid membrane electrodes having membranes formed from an organic solution containing an electrically neutral, ion-selective agent such as an ionophore held in an inert polymer matrix.
Conventional ISE sensors are typically bulky and tend to require an undesirable large volume of biological fluid. For these reasons, much attention has been directed towards developing ISE sensors of smaller size. These relatively smaller ISE sensors can be inexpensively mass produced using techniques similar to those employed in the manufacture of multilayer electronic components, which techniques include for example, photolithography and screen printing as described in U.S. Pat. No. 4,454,007. Such ISE sensors may be in the form of a disposable cartridge or sensor assembly for use in an chemical analyzer and are generally produced on a planar substrate with plural reference elements and plural sensor elements formed thereon. Electrical contacts are positioned on the substrate face for each element, and a flow channel is typically positioned over the substrate reference and sensor elements to direct the sample being analyzed over the sensor elements. Liquid conduits are adapted to supply biological samples to the flow channel and to remove them from the ISE sensor device. The ISE sensor substrate is advantageously chosen to be of a structurally rigid material that exhibits negligible distortion when pressure is applied from the flow channel member, and is an electrical insulator to provide support for the layers of a multilayer ion sensor. A preferred material for the substrate is alumina.
The manufacture of a complete ISE sensor includes numerous sequential manufacturing steps in which the patterns within adjacent layers produced during successive manufacturing process must be aligned properly with patterns produced by preceding processes. These successive manufacturing steps are fairly complex in nature and may include conventional screen printing using a screening or photographic mask, and firing processes of paste-like compositions to produce the desired performance. The pattern and structure of the sensor resulting from each step of these many sequential operations must be accurately aligned with patterns and structures generated in preceding process steps. A misregistration of a single operation may result in an electrical open or short circuit in the finished sensor.
The use of finer and finer grids and closely spaced features as found in modern ISE sensors requires a very high degree of positional accuracy of imprinted features. Consequently, misregistration of pattern features on the panels that may occur from misalignment of the panel and screening mask or machine tool in any singular step of the multi-step manufacturing process is a particularly critical problem in contributing to manufacturing yields. Due to the importance of maintaining correct registration of all the features generated by the sequence of manufacturing steps throughout the manufacturing process, modern ISE sensors must be inspected frequently at various stages of their manufacturing.
In order to improve the accuracy of inspection during sequential manufacturing of multilayer devices in mass produced quantities, machine vision systems are frequently employed. Machine vision systems acquire an image of a selected portion of the device through an electronic sensor and determine the existence of any extraneous features or marks in the image and the acceptability of any such marks by use of a computer. The technology commonly employs a solid state CCD (charge coupled device) or MOS (metal oxide semiconductor) type black and white or color television camera. Other components of a machine vision system normally include a lens that is attached to the television camera, as well as mirrors, beam splitters (partially silvered mirrors that can reflect and transmit light at the same time), color filters, polarizers, etc. These additional components can be used to enhance contrast and/or to reduce the effect of unwanted information, to obtain the needed optical geometric arrangement in a limited space, to acquire the image, to acquire and store a two-dimensional image, and to process and analyze the image by some form of computer. Machine vision systems can also provide important and accurate process control information to help identify "problem area(s)" of the sequential manufacturing process so they may be corrected to improve quality and yield.
In the design of ISE sensors, many of the solid membranes that are selective to the ionic species being sought comprise a polymeric membrane composition that is essentially optically undistinguished from a surrounding or underlying material, i.e., is translucent, is semi-transparent, or has an optical reflectivity essentially similar to that of the surrounding material. Consequently, the integrity, pattern and outline of the imprinted membrane layer pattern may not be readily differentiated by machine vision systems. In such instances, it is known to tag the material to be identified using fluorescent compounds that are more readily capable of detection. The use of fluorescent techniques to detect the presence of compounds is known in the art. With fluorescent scanning, tagged samples are stimulated by a light beam at an excitation wavelength and the resulting stimulated fluorescent emission is examined. The stimulated fluorescent typically occurs at a different wavelength or wavelength band than the excitation wavelength. See, for example, U.S. Pat. No. 5,459,325, "High Speed Fluorescent Scanner", Hueton et als. A light source which is capable of emitting light in the near-infrared illuminates the material to be inspected and an optical filter is used to select only the wavelengths emitted by the tagging fluorescing compound.
U.S. Pat. No. 4,983,817 relates to reading a luminescent and substantially transparent bar code on a background whose reflectance may vary. Electrical signals corresponding to light reflections from both luminescent and non-luminescent portions of the bar code are processed to provide a final signal that is decoded to provide the desired reading.
U.S. Pat. No. 4,186,020 describes development of fluorescent inks that can be activated by ultraviolet light to fluoresce at longer wavelengths in instances when the background fluorescence is less.
U.S. Pat. No. 5,095,204 presents a system and method for treating or modifying bulk materials or formed articles such that they can be seen and identified under ultraviolet radiation without a permanent alteration of their appearance or properties.
U.S. Pat. No. 5,461,136 relates to a method for "marking" or "tagging" a thermoplastic polymeric material by incorporating one or more near infrared fluorescing compounds therein and a method for separating or sorting a mixture of thermoplastic containers such as bottles. Also provided are thermoplastic polymer compositions tagged with such compounds or residues as well as certain new compounds useful as near infrared fluorophoric markers.
However, a shortcoming in the application of conventional machine vision systems to the inspection of sensor membranes is the degradation in performance of the sensor membranes due to the inclusion of fluorescing compounds to make them optically discernible. The selectivity and sensitivity of an ISE sensor membrane are critically dependent upon its chemical constituents and their relative balances. Consequently, there has developed a need for a chemically inert ingredient such as a fluorophore which may be added to the sensor membrane in a quantity that does not interfere with the analytical performance of the sensor but which provides the needed fluorescence to distinguish properly aligned layers as well as identify membrane defects resulting from the manufacturing process.